The broad objective of the proposed research is to test the hypothesis that elimination of all or most of the patient's HIV infected cells and replacement of these cells with transplanted hematopoietic stem cell resistant to HIV infection, could serve as an effective treatment for AIDS patients. This hypothesis will be tested by means of anti-sense gene therapy utilizing genetically augmented hematopoietic stem cell progenitors (yolk-sac cells) in a murine retrovirus infected mouse model system using Moloney murine Leukemia virus (M-MuLV). First, anti-sense ribozyme expressing transgenic mice will be compared to determine the relative effectiveness of these anti-viral agents in inhibiting M-MuLV viremia. Then, gene therapy of M-MuLV infected normal mice with anti-sense and anti- sense ribozyme RNA expressing genes will be attempted. Following partial ablation of their bone marrow, infected mice will receive a transplant of cultured yolk-sac cells expressing either of the anti-viral anti-sense RNAs and mutant dihydrofolate reductase enzyme to impart resistance to the chemotherapeutic drug methotrexate. After receiving transplanted, anti- sense expressing, yolk-sac cells, the recipient mice will be maintained or a continuous dose of methotrexate to destroy the remaining recipient hematopoietic cells and select for the transplanted cells. Mice receiving this therapeutic regiment will be assayed for their level of M-MuLV viremia for several months following treatment.